CANCER GENOMICS AND EPIGENOMICS: SUMMARY The overarching goal of the Cancer Genomics and Epigenomics (CGE) Program is to define the mechanisms, both genetic and epigenetic, that preserve genome integrity in normal cells and elicit genome instability in cancer cells. The CGE Program is led by Jean Gautier, PhD and Raul Rabadan, PhD who have complementary expertise in experimental and computational cancer biology. The CGE Program, which was founded in 2008, has 41 Members representing 13 departments across three different schools at Columbia University. The scientific goals of the CGE Program are achieved through three interrelated Specific Aims: (1) Genome Plasticity: To evaluate how normal and pathological pathways of DNA repair contribute to the genomic instability associated with cancer; (2) Epigenetics: To determine how changes in chromatin modification and organization promote tumor development; and 3. Computational Genomics and Genetics: To develop and implement multiscale, genome-wide strategies to identify the genomic aberrations that drive cancer development. In particular, CGE Members continue to provide pivotal insights into how DNA repair, a critical tumor suppression mechanism, is essential for maintenance of genome stability. Furthermore, following major strategic investments in cancer genomics and epigenomics, CGE Members work at the forefront of research in several tumor types, including ALL, PTCL, DLBCL and glioblastoma, with strong computational biology collaborations. The CGE Program addresses research relevant to the HICCC Catchment Area by focusing on triple-negative breast cancer and peripheral T cell lymphoma. In turn, the HICCC facilitates CGE research and development by supporting internal pilot studies, multi-investigator grants proposals, strategic faculty recruitments, and use of Shared Resources. Consequently, the CGE Program maintains a strong portfolio of intra- and inter- programmatic multi-investigator grants, which includes existing NCI-funded programs that anchor both Aim 1 (P01-CA174653; DNA double-strand break repair, chromosomes translocations and cancer) and Aim 3 (U54- CA193313, Topology of cancer evolution and heterogeneity), as well as a developing epigenetics program project aligned with Aim 2. The CGE Members contribute to the daily operation of multiple HICCC Shared Resources and participate actively in cancer training at all levels. Finally, the computational/mathematical genomics research of CGE Members continues to have a growing impact across all HICCC activities, encompassing the full spectrum of basic, translational, clinical and population research. In 2018, 41 program members had a total of $16M in cancer-focused, peer-reviewed funding (direct costs), of which $9.2M (57%) was from NCI, $4.8M (30%) from other NIH sources, and $1.9M (12%) from other peer- review agencies. During the current project period, CGE Members authored a total of 959 cancer-relevant publications, of which 112 (12%) were intra-programmatic and 202 (21%) inter-programmatic. Notably, 29% of these CGE publications appeared in journals with impact factors >10.